Cinacalcet Increases Calcium Excretion in Hypercalcemic Hyperparathyroidism After Kidney Transplantation

Background. Cinacalcet reduces serum calcium in kidney transplant recipients with hypercalcemic hyperparathyroidism. The mechanism of action is not fully understood. We hypothesized that cinacalcet increases renal elimination of calcium, thereby improving hypercalcemia in kidney transplant recipients. Methods. We prospectively examined the effect of cinacalcet (30 mg/d) during the first 6 weeks of treatment on serum and 24 hrs urinary calcium concentration and calculated fractional calcium excretion in 32 patients with sustained hypercalcemic hyperparathyroidism (Ca > 2.6 mmol/L [10.4 mg/dL], intact parathyroid hormone > 60 pg/mL). Secondary endpoints were serum phosphate and tubular maximum of phosphate corrected for glomerular filtration rate, intact parathyroid hormone and serum creatinine. Results. Serum calcium concentrations decreased in all patients (from 2.77 to 2.51 mmol/L; P < 0.0001), fractional calcium excretion increased rapidly in the first 2 weeks of treatment from 1.06 to 1.78% (P < 0.0001), and decreased thereafter to 1.37% (P < 0.05 vs. early treatment). Simultaneously serum phosphate and tubular maximum of phosphate corrected for glomerular filtration rate increased significantly from 0.79 to 0.85 to 0.88 mmol/l, (P < 0.05), and from 0.52 to 0.61 (P < 0.005) and 0.62 (P < 0.0001 vs. baseline), respectively. Intact parathyroid hormone did not decrease significantly. Serum creatinine remained stable. Conclusion. We provide evidence that the calcium lowering effect of cinacalcet in patients with persistent hyperparathyroidism after kidney transplantation is caused, at least in part, by increased urinary calcium excretion.